AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions--agency for healthcare research and quality and the effective health-care program.

OBJECTIVE: To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality. STUDY DESIGN AND
SETTING: Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group.
RESULTS: The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose-response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence.
CONCLUSION: EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence.